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Abatacept as a long-term targeted therapy for LRBA deficiency
(Elsevier, 2019-12) Kiykim, Ayça; Ogulur, İsmail; Dursun, Esra; Dogruel, Dilek; Karaca, Neslihan Edeer; Cogurlu, Mujde Tuba; Bilir, Ozlem Arman; Cansever, Murat; Kapakli, Hasan; Baser, Dilek; Kasap, Nurhan; Kutlug, Seyhan; Altintas, Derya Ufuk; Al-Shaibi, Ahmad; Agrebi, Nourhen; Kara, Manolya; Guven, Ayla; Somer, Ayper; Aydogmus, Cigdem; Ayaz, Nuray Aktay; Metin, Ayse; Aydogan, Metin; Uncuoglu, Aysen; Patiroglu, Turkan; Yildiran, Alisan; Guner, Sukru Nail; Keles, Sevgi; Reisli, Ismail; Aksu, Guzide; Kutukculer, Necil; Yilmaz, Mustafa; Karakoc-Aydiner, Elif; Lo, Bernice; Ozan, Ahmet; Chatila, Talal A.; Barıs, Safa; Çekiç, Şükrü; Kılıç, Sara Şebnem; Uludağ Üniversitesi/Tıp Fakültesi/Dahili Bilimler/Çocuk Sağlığı ve Hastalıkları; Uludağ Üniversitesi/Tıp Fakültesi/Dahili Bilimler/Çocuk Sağlığı ve Hastalıkları; 0000-0002-9574-1842; 0000-0001-8571-2581; L-1933-2017; 57094682600; 7102365439
BACKGROUND: LPS-responsive beige-like anchor (LRBA) deficiency presents with susceptibility to infections, autoimmunity, and lymphoproliferation. The long-term efficacy of cytotoxic T-lymphocyte-associated antigen 4-immunoglobulin (abatacept) as targeted therapy for its immune dysregulatory features remains to be established. OBJECTIVE: To determine the clinical and immunologic features of LRBA deficiency and long-term efficacy of abatacept treatment in controlling the different disease manifestations. METHODS: Twenty-two LRBA-deficient patients were recruited from different immunology centers and followed prospectively. Eighteen patients on abatacept were evaluated every 3 months for long-term clinical and immunologic responses. LRBA expression, lymphocyte subpopulations, and circulating T follicular helper cells were determined by flow cytometry. RESULTS: The mean age of the patients was 13.4 +/- 7.9 years, and the follow-up period was 3.4 +/- 2.3 years. Recurrent infections (n = 19 [86.4%]), immune dysregulation (n = 18 [81.8%]), and lymphoproliferation (n = 16 [72.7%]) were common clinical features. The long-term benefits of abatacept in 16 patients were demonstrated by complete control of lymphoproliferation and chronic diarrhea followed by immune dysregulation, most notably autoimmune cytopenias. Weekly or every other week administration of abatacept gave better disease control compared with every 4 weeks. There were no serious side effects related to the abatacept therapy. Circulating T follicular helper cell frequencies were found to be a reliable biomarker of disease activity, which decreased on abatacept therapy in most subjects. However, high circulating T follicular helper cell frequencies persisted in 2 patients who had a more severe disease phenotype that was relatively resistant to abatacept therapy. CONCLUSIONS: Long-term abatacept therapy is effective in most patients with LRBA deficiency.
ABO and RhD blood groups and their relationship with diseases: A retrospective study
(Professional Medical Publications, 2024-03) Göktaş, Olgun; Göktaş, Olgun; Uludağ Üniversitesi/Aile Sağlığı Merkezi; EXQ-8413-2022
Objective: To retrospectively evaluate the distribution of ABO and RhD blood groups and their relationship with diseases. Methods: The retrospective study was carried out in Bursa Uludag University Family Health Center in Turkey between 1-28 February, 2023. The data of individuals who were registered with the Family Health Center and whose blood types were known were evaluated retrospectively. Blood group type, sociodemographic findings, existing diseases, allergies, and genetic disease conditions were obtained. P-values below 0.05 were considered statistically significant. Analysis were made in the SPSS 25.0 program. Results: A total of 3834 people, 1935 male (50.5%) and 1899 female (49.5%) participated in the study. The mean age of the individuals was 26.45 +/- 10.45 years. About 75.8 percent of the participants were university students, 6.3 percent were health workers, and 17.9 percent were from other occupational groups. The rates of blood groups were determined as O Rh D+ at 33.5%, AB Rh D+ at 26.9%, A Rh D+ at 14.9%, AB Rh D- at 7.7%, B Rh D+ at 7%, O Rh D- at 4.6%, B Rh D- at 3.2% and A Rh D- at 2.2%. It was determined that the O Rh D- group had a higher rate of genetic disease than the other groups (p=0.01). Conclusion: It was determined that the O Rh D+ blood group was found more frequently in our region's population than in other groups. This different result depending on the A Rh D+ blood group, which is the most common throughout the country may have reflected the influence of different geographical regions and ethnic characteristics due to the students in our population. In addition, the results regarding the relationships between blood groups and occupation, genetics, existing disease, presence of allergies, and visual defects in the eye are important.
Advances and recent developments in asthma in 2020
(Wiley, 2020-09-30) Cevhertaş, Laçin; Bursa Uludağ Üniversitesi/Tıp Fakültesi/İmmünoloji Anabilim Dalı.; 0000-0003-2287-3569; 57216918051
In this review, we discuss recent publications on asthma and review the studies that have reported on the different aspects of the prevalence, risk factors and prevention, mechanisms, diagnosis, and treatment of asthma. Many risk and protective factors and molecular mechanisms are involved in the development of asthma. Emerging concepts and challenges in implementing the exposome paradigm and its application in allergic diseases and asthma are reviewed, including genetic and epigenetic factors, microbial dysbiosis, and environmental exposure, particularly to indoor and outdoor substances. The most relevant experimental studies further advancing the understanding of molecular and immune mechanisms with potential new targets for the development of therapeutics are discussed. A reliable diagnosis of asthma, disease endotyping, and monitoring its severity are of great importance in the management of asthma. Correct evaluation and management of asthma comorbidity/multimorbidity, including interaction with asthma phenotypes and its value for the precision medicine approach and validation of predictive biomarkers, are further detailed. Novel approaches and strategies in asthma treatment linked to mechanisms and endotypes of asthma, particularly biologicals, are critically appraised. Finally, due to the recent pandemics and its impact on patient management, we discuss the challenges, relationships, and molecular mechanisms between asthma, allergies, SARS-CoV-2, and COVID-19.
Alpha v beta 3 integrin antagonists enhance chemotherapy response in an orthotopic pancreatic cancer model
(Frontiers Media, 2020-01-27) Sudha, Thangirala; Bharali, Dhruba J.; Davis, Paul J.; Mousa, Shaker A.; Coşkun, Melis Debreli; Çelikler, Serap; Bursa Uludağ Üniversitesi/Fen-Edebiyat Fakültesi/Biyoloji Bölümü.; 0000-0002-4177-3478; CML-2517-2022; 57194630463; 8234554800
Pancreatic cancer decreases survival time and quality of life because of drug resistance and peripheral neuropathy during conventional treatment. This study was undertaken to investigate whether alpha v beta 3 integrin receptor antagonist compounds NDAT and XT199 can suppress the development of cisplatin resistance and cisplatin-induced peripheral neuropathy in an orthotopic pancreatic SUIT2-luc cancer cell mouse model. Anticancer effects of these compounds and their combination with cisplatin were assessed in this tumor mouse model with bioluminescent signaling and histopathology, and a cytokine assay was used to examine expression of inflammatory cytokines IL-1 beta, IL-6, IL-10, and TNF-alpha from plasma samples. To determine the neuroprotective effects of the compounds on cisplatin-induced peripheral neuropathy, behavioral hind-limb posture of the mice was evaluated. The combination therapy of NDAT or XT199 with cisplatin elicited greater inhibition of tumor growth and increased tumor necrosis compared to cisplatin alone. NDAT and XT199 in combination with cisplatin significantly decreased expression of pro-inflammatory cytokines IL-1 beta, IL-6, and TNF-alpha and significantly increased expression of anti-inflammatory cytokine IL-10 in comparison to cisplatin alone. Cisplatin-treated groups showed stocking-glove hind-limb posture, whereas NDAT and XT199 with cisplatin-treated groups displayed normal hind-limb posture. Results clearly suggest that NDAT and XT199 treatment with cisplatin that inactivates NF-kappa B may contribute to increased antitumor and anti-inflammatory efficacy as well as alleviate cisplatin-mediated loss of motor function in this pancreatic tumor mouse model.
Amplitude analysis of d-s(+) -> pi(+)pi(0)eta and first observation of the w-annihilation dominant decays d-s(+) -> a(0)(980)(+)pi(0) and d-s(+) -> a(0)(980)(0)pi(+)
(American Physical Society, 2019-09-12) Yan, Wenbiao; Bursa Uludağ Üniversitesi.; 35770088900
We present the first amplitude analysis of the decay D-s(+) -> pi(+)pi(0)eta. We use an e(+)e(-) collision data sample corresponding to an integrated luminosity of 3.19 fb(-1) collected with the BESIII detector at a center-of-mass energy of 4.178 GeV. We observe for the first time the W-annihilation dominant decays D-s(+) -> a(0)(980)(+)pi(0) and D-s(+) -> a(0)(980)(0)pi(+). We measure the absolute branching fraction B(D-s(+) -> a(0)(980)(+(0))pi(0(+)), a(0)(980)(+(0)) -> pi(+(0))eta = (1.46 +/- 0.15(stat) +/- 0.23 sys)%, which is larger than the branching fractions of other measured pure W-annihilation decays by at least one order of magnitude. In addition, we measure the branching fraction of D-s(+) -> pi(+)pi(0)eta with significantly improved precision.
Anatomical study of the cavernous sinus emphasizing operative approaches
(Türk Nöroşirürji Derneği, 2010-04) Boyacı, Suat; Aksoy, Kaya; Dalgıç, Adem; Uludağ Üniversitesi/Tıp Fakültesi/Beyin ve Sinir Cerrahisi Anabilim Dalı.; 36135211700
AIM: The aim of this article is to describe the microsurgical anatomy of the cavernous sinus, the triangles, and the osseous relationships in the region with special attention to the relationships important in surgical approaches on the intracavernous structures. MATERIAL and METHODS: Fifty cavernous sinuses obtained from twenty-five cadaver heads were studied in detail using magnification. Stepwise dissections of the cavernous sinuses performed to demonstrate the intradural and extradural routes, anatomy of the triangles and osseous relationships in the region. RESULTS: The main branches of the intracavernous portion of the carotid artery were the meningohypophyseal, the inferior cavernous sinus, and McConnell's capsular artery. The main branches of the meningohypophyseal trunk were the tentorial, the dorsal meningeal, and the inferior hypophyseal artery. There were variations of the main branches of the meningohypophyseal trunk. The sixth cranial may splite into rootlets as it passes lateral to the carotid artery. There were size and shape variation of the triangles. CONCLUSION: A precise understanding of the bony relationships, the anatomy of the triangels and neurovascular content of the cavernous sinus, together with the use of cranial base and microsurgical techniques are necessary for safer surgery. A single approach is not capable of providing exposure of all parts of the sinus.
Angiotensin-II receptor antagonist losartan reduces micro albuminuria in hypertensive renal transplant recipients
(Wiley, 2002-06) Alparslan, Ersoy; Dilek, Kamil; Usta, Mehmet; Yavuz, Mahmut; Güllülü, Mustafa; Yurtkuran, Mustafa Abbas; Oktay, Burçin; Uludağ Üniversitesi/Tıp Fakültesi/Nefroloji Anabilim Dalı.; 0000-0002-0710-0923; AAH-5054-2021; 35612977100; 56005080200; 7005030712; 7006244754; 6602684544; 6602172127; 7003389525
In recent years, it has been demonstrated that losartan lowers macroproteinuria in diabetic or non-diabetic renal transplant recipients (RTx) similar to angiotensin converting enzyme (ACE) inhibitors. Microalbuminuria (MAU) may reflect subclinical hyperfiltration damage of the glomerulus. It could be a marker of kidney dysfunction in renal transplantation. The aim of the study was to assess the efficacy of losartan in hypertensive RTx with MAU. This study was conducted in 17 (M/F: 4/13) stable RTx. No change was made in the medical treatment of the patients. All cases received 50 mg/day losartan therapy for 12 wk. Renal functions and MAU were determined 12 and 6 wk and just before the treatment as well as sixth and twelfth week of the treatment in all patients. Losartan satisfactorily lowered systemic blood pressure. A significant reduction in MAU was observed from 103 +/- 53 mug/min at the beginning to 59 +/- 25 mug/min in the sixth week and 47 +/- 24 mug/min in the twelfth week (p = 0.0007 and 0.0005, respectively). From the sixth week of the treatment, the therapy significantly decreased hemoglobin, hematocrit and erythrocyte levels but did not change mean leukocyte and platelet counts, urea, creatinine levels and creatinine clearances. No serious side-effect was observed,during the study. In conclusion, we found that losartan decreased MAU in hypertensive RTx. For that reason, it might be considered as the first choise antihypertensive agent for the renoprotection in selected patients.
Anti-tumour necrosis factor-alpha treatment of juvenile idiopathic arthritis in a patient with common variable immunodeficiency
(Oxford University Press, 2005-06) Kılıç, Sara Şebnem; Uludağ Üniversitesi/Tıp Fakültesi/Çocuk Sağlığı ve Hastalıkları Anabilim Dalı.; 0000-0001-8571-2581; AAH-1658-2021; 34975059200
Antibiotic overconsumption and resistance in Turkey
(Elsevier Science, 2019-06) Keske, S.; Aksoy, M.; Azap, O. K.; Yilmaz, M.; Yavuz, S. S.; Aygun, G.; Tigen, E.; Azap, A.; Ergonul, O.; Isler, B.; Akalın, Halis; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Dahili Tıp Bilimleri/Enfeksiyon Hastalıkları ve Klinik Mikrobiyoloji Anabilim Dalı.; AAU-8952-2020; 57207553671
Antituberculosis drug resistance patterns in adults with tuberculous meningitis: Results of Haydarpasa-iv study
(BMC, 2015-11-04) Yılmaz, Emel; Uludağ Üniversitesi/Tıp Fakültesi/Enfeksiyon Hastalıkları ve Klinik Mikrobiyoloji Anabilim Dalı.; HJZ-6992-2023; 22037135100
Background: Tuberculous meningitis (TBM) caused by Mycobacterium tuberculosis resistant to antituberculosis drugs is an increasingly common clinical problem. This study aimed to evaluate drug resistance profiles of TBM isolates in adult patients in nine European countries involving 32 centers to provide insight into the empiric treatment of TBM. Methods: Mycobacterium tuberculosis was cultured from the cerebrospinal fluid (CSF) of 142 patients and was tested for susceptibility to first-line antituberculosis drugs, streptomycin (SM), isoniazid (INH), rifampicin (RIF) and ethambutol (EMB). Results: Twenty of 142 isolates (14.1 %) were resistant to at least one antituberculosis drug, and five (3.5 %) were resistant to at least INH and RIF, [multidrug resistant (MDR)]. The resistance rate was 12, 4.9, 4.2 and 3.5 % for INH, SM, EMB and RIF, respectively. The monoresistance rate was 6.3, 1.4 and 0.7 % for INH, SM and EMB respectively. There was no monoresistance to RIF. The mortality rate was 23.8 % in fully susceptible cases while it was 33.3 % for those exhibiting monoresistance to INH, and 40 % in cases with MDR-TBM. In compared to patients without resistance to any firstline drug, the relative risk of death for INH-monoresistance and MDR-TBM was 1.60 (95 % CI, 0.38-6.82) and 2.14 (95 % CI, 0: 34-13: 42), respectively. Conclusion: INH-resistance and MDR rates seemed not to be worrisome in our study. However, considering their adverse effects on treatment, rapid detection of resistance to at least INH and RIF would be most beneficial for designing anti-TB therapy. Still, empiric TBM treatment should be started immediately without waiting the drug susceptibility testing.
Antiviral therapy in neonatal cholestatic cytomegalovirus hepatitis
(BMC, 2007-03-13) Dikici, Bünyamin; Mıstık, Reşit; Özkan, Tanju Başarır; Nazlıoğlu, Hülya Öztürk; Uludağ Üniversitesi/Tıp Fakültesi/Patoloji Anabilim Dalı.; Uludağ Üniversitesi/Tıp Fakültesi/Çocuk Sağlığı ve Hastalıkları Anabilim Dalı.; Uludağ Üniversitesi/Tıp Fakültesi/İnfeksiyon Hastalıkları ve Klinik Mikrobiyoloji Anabilim Dalı Başkanlığı.; 0000-0001-7572-6525; 7004474005; 6602564624; 57197115377
Background: Neonatal hepatitis refers to a heterogeneous group of disorders, caused by many factors including cytomegalovirus infection, revealing similar morphologic changes in the liver of an infant less than 3 months of age. Approximately 40% of cholestasis in infants is due to neonatal hepatitis. It may cause latent or acute cholestatic or chronic hepatitis, including cirrhosis in immunocompetant infant. Methods: Twelve infants diagnosed with neonatal cytomegalovirus hepatitis in the last one year were included in the study. Group 1 consisted of seven babies treated with ganciclovir for 21 days. Group 2 included five cases who did not receive antiviral treatment. Physical examination, biochemical, serologic and virologic tests were done for both groups at the time of diagnosis and in the third month. Results: Initial levels of total bilirubin, aminotransferases, gamma glutamyl transpeptidase, and alkaline phosphatase revealed a significant decrease after the treatment in Group 1 ( p < 0.05) when compared with Group 2. This study revealed that ganciclovir treatment is a safe and effective in cases with cholestatic hepatitis. Similarly, all the patients in the treatment group had evidence of improvement serologically and virologically, while the comparison group did not reveal any significant change( p < 0.01). Conclusion: The clinical spectrum of perinatal infection varies from an asymptomatic infection or a mild disease to a severe systemic involvement, including central nervous system. The treatment in the early period of infection improved serologic markers and cholestatic parameters significantly. Further studies will lead us to clarify the efficacy of ganciclovir treatment in the early period of cytomegalovirus hepatitis, and the preventive role of anti-viral therapy on progressive liver disease due to cholestasis and hepatitis in neonatal cytomegalovirus infection.
Arterial tortuosity syndrome: 40 new families and literature review
(Nature Publishing Group, 2018-01-11) Bostan, Özlem Mehtap; Temel, Şehime Gülsün; Uysal, Fahrettin; Uludağ Üniversitesi/Tıp Fakültesi/Pediatrik Kardiyoloji Anabilim Dalı.; Uludağ Üniversitesi/Tıp Fakültesi/Histoloji ve Embriyoloji Anabilim Dalı.; Uludağ Üniversitesi/Tıp Fakültesi/Tıbbi Genetik Anabilim Dalı.; 0000-0001-7707-2174; 0000-0002-9802-0880; AAG-8558-2021; AAG-8385-2021; AAH-4421-2021; 8676936500; 6507885442; 24469008200
Purpose: We delineate the clinical spectrum and describe the histology in arterial tortuosity syndrome (ATS), a rare connective tissue disorder characterized by tortuosity of the large and medium-sized arteries, caused by mutations in SLC2A10. Methods: We retrospectively characterized 40 novel ATS families (50 patients) and reviewed the 52 previously reported patients. We performed histology and electron microscopy (EM) on skin and vascular biopsies and evaluated TGF-beta signaling with immunohistochemistry for pSMAD2 and CTGF. Results: Stenoses, tortuosity, and aneurysm formation are widespread occurrences. Severe but rare vascular complications include early and aggressive aortic root aneurysms, neonatal intracranial bleeding, ischemic stroke, and gastric perforation. Thus far, no reports unequivocally document vascular dissections or ruptures. Of note, diaphragmatic hernia and infant respiratory distress syndrome (IRDS) are frequently observed. Skin and vascular biopsies show fragmented elastic fibers (EF) and increased collagen deposition. EM of skin EF shows a fragmented elastin core and a peripheral mantle of microfibrils of random directionality. Skin and end-stage diseased vascular tissue do not indicate increased TGF-beta signaling. Conclusion: Our findings warrant attention for IRDS and diaphragmatic hernia, close monitoring of the aortic root early in life, and extensive vascular imaging afterwards. EM on skin biopsies shows disease-specific abnormalities.
Assessment of health-related quality of life in pediatric acute lymphoblastic leukemia survivors: Perceptions of children, siblings, and parents
(Galenos Publishing House, 2019) Kızmazoğlu, Deniz; Sarı, Seher; Tüfekçi, Özlem; Yenigürbüz, Fatma Demir; Yılmaz, Şebnem; Ören, Hale; Sezgin, Melike Evim; Kantarcıoğlu, Arzu; Baytan, Birol; Güneş, Adalet Meral; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Dahili Tıp Bilimleri/Çocuk Sağlığı Ve Hastalıkları Bölümü; DRM-9969-2022; ILH-2286-2023; DVW-8108-2022; JGX-6145-2023; 57208701966; 55317096200; 6506622162; 24072843300
Objective: We investigated the health-related quality of life (HRQL) in survivors of pediatric acute lymphoblastic leukemia (ALL) and evaluated the perceptions of the children, their siblings, and their parents. Materials and Methods: Seventy ALL survivors, who were between 7 and 17 years of age and had completed therapy ≥2 years, were included. The control group consisted of their healthy siblings. HRQL was assessed by the age-specific KINDLR questionnaire. Results: No significant differences could be found among HRQL scores of ALL survivors with respect to variables such as sex, risk group, and having chronic illness. HRQL scores for physical well-being, emotional well-being, family, and social functioning of the patient and sibling self-reports and parent proxy reports were lower than the expected values for healthy and chronically ill children. Conclusion: These results demonstrate that both ALL survivors and their families need help via psychological counseling programs to improve their HRQL even after completion of therapy. Keywords: Acute lymphoblastic leukemia, Health-related quality of life, KINDLR questionnaire
Assessment of the requisites of microbiology based infectious disease training under the pressure of consultation needs
(BMC, 2011) Erdem, Hakan; Koruk, Suda Tekin; Koruk, İbrahim; Keten, Derya Tozlu; Kılıç, Aysegül Ulu; Öncül, Oral; Güner, Rahmet; Birengel, Serhat; Mert, Gürkan; Alpat, Saygın Nayman; Tülek, Necla Eren; Demirdal, Tuna; Elaldi, Nazif; Hatipoglu, Çiğdem Ataman; Yılmaz, Emel; Mete, Bilgul; Kurtaran, Behice; Ceran, Nurgül; Karabay, Oğuz; İnan, Dilara; Cengiz, Melahat; Sacar, Suzan; Dede, Behiye Yücesoy; Yılmaz, Sibel; Agalar, Canan; Bayındır, Yaşar; Alpay, Yeşim; Tosun, Selma; Yılmaz, Hava; Bodur, Hürrem; Erdem, Hüseyin A.; Dikici, Nebahat; Dizbay, Murat; Öncu, Serkan; Sezak, Nurbanu; Sarı, Tuba; Sipahi, Oğuz R.; Uysal, Serhat; Yeniz, Esma; Kaya, Selcuk; Ulcay, Asım; Kurt, Halil; Beşirbellioğlu, Bulent A.; Vahaboğlu, Haluk; Taşova, Yeşim; Usluer, Gaye; Arman, Dilek; Diktaş, Hüsrev; Ulusoy, Sercan; Leblebicioğlu, Hakan; Yılmaz, Emel; Uludağ Üniversitesi/Tıp Fakültesi/Enfeksiyon Hastalıkları ve Klinik Mikrobiyoloji Anabilim Dalı.; 0000-0002-3894-1231; 22037135100
Background: Training of infectious disease (ID) specialists is structured on classical clinical microbiology training in Turkey and ID specialists work as clinical microbiologists at the same time. Hence, this study aimed to determine the clinical skills and knowledge required by clinical microbiologists. Methods: A cross-sectional study was carried out between June 1, 2010 and September 15, 2010 in 32 ID departments in Turkey. Only patients hospitalized and followed up in the ID departments between January-June 2010 who required consultation with other disciplines were included. Results: A total of 605 patients undergoing 1343 consultations were included, with pulmonology, neurology, cardiology, gastroenterology, nephrology, dermatology, haematology, and endocrinology being the most frequent consultation specialties. The consultation patterns were quite similar and were not affected by either the nature of infections or the critical clinical status of ID patients. Conclusions: The results of our study show that certain internal medicine subdisciplines such as pulmonology, neurology and dermatology appear to be the principal clinical requisites in the training of ID specialists, rather than internal medicine as a whole.
Association of breast cancer and cytokine gene polymorphism in Turkish women
(Saudi Medical Journal, 2007-11) Gönüllü, Güzin; Baştürk, Bilkay; Evrensel, Türkkan; Oral, Barbaros; Gözkaman, Ayşe; Manavoğlu, Osman; Uludağ Üniversitesi/Tıp Fakültesi/Onkoloji Anabilim Dalı.; Uludağ Üniversitesi/Tıp Fakültesi/Immünoloji Anabilim Dalı.; 6603942124; 7004498001; 9633205800; 6602587152
Objective: To investigate the association of cytokine gene polymorphism with the development of breast cancer. Methods: The study was carried out in Uludag University Medical School, Bursa, Turkey. The study included 38 patients with breast cancer admitted to the Medical Oncology outpatient clinic, and 24 healthy controls, age and sex matched, from the Internal Medicine Department between 2004 and 2005. All genotyping of tumor necrosis factor-cc (TNF-alpha), tumor growth factor-beta 1 (TGF-beta 1), interleukin (IL)-10, IL-6, and interferon-gamma (IFN-gamma) experiments were performed using polymerase chain reaction sequence-specific primers. Results: The frequencies of IL-6-174GC genotype and IL-10 (-1082, -819, -592) GCC/ATA haplotype were significantly higher in the patient group (p=0.0008) when compared with controls (p=0.020). Significantly lower frequencies of IL-10 (-1082,-819,-592) ACC/ATA haplotype were observed in the patient group in comparison to the controls (p=0.026). The distribution of IFN-gamma +874, TNF-a 308, and TGF-beta 1 codon 10-25 genotypes failed to show any statistical significant association with the development of breast cancer. Conclusion: Our data suggest that IL-10 (-1082, -819, -592) GCC/ATA haplotype and IL-6-174 GC genotype seem to be potential risk factors for the development of breast cancer. The presence of IL-10ACC/ATA haplotype may be protective for the oncogenesis of breast cancer.
Basic interrupted versus continuous suturing techniques in bronchial anastomosis following sleeve lobectorny in dogs
(Oxford University Press, 2007-09-03) Erol, Mehmet Muharrem; Bayram, Ahmet Sami; Salcı, Hakan; Özyiǧit, Özgür M.; Görgül, Sacit O.; Gebitekin, Cengiz; Uludağ Üniversitesi/Tıp Fakültesi/Göğüs Cerrahisi Anabilim Dalı.; Uludağ Üniversitesi/Veteriner Fakültesi/Cerrahi Anabilim Dalı.; 0000-0003-0684-0900; 8347194000; 8680329000; 22954215300; 22953784900; 6602156436
Objective: Sleeve resection with or without lung resection is a valid conservative operation for patients with benign or malignant tumors; it enables the preservation of lung parenchyma. The aim of this prospective randomized study was to compare complications, operating time, and bronchial heating between the techniques of interrupted and continuous suturing for bronchial anastomosis in dogs. Methods: Twenty adult mongrel dogs each weighing 18-22 kg (average: 20 kg) were divided into two groups according to the anastomosis technique performed: group A, interrupted suturing and group B, continuous suturing. Each group comprised of 10 dogs. Following right thoracotomy, sleeve resection of the right cranial lobe was performed in all dogs. Basic interrupted sutures using 4/0Vicryl (Ethicon, USA)were used in group A, and continuous sutures were used in group B. Results: The median anastomosis time was 15.2 min (range: 13-21 min) in group A and 9.6 min (range: 8-13 min) in group B. In all dogs, the anastomosis line was resected via right pneumonectomy for histopathological investigation 1 month after sleeve resection. Histopathological examination revealed that the healing of the anastomosis was not affected by the suturing technique applied. One dog from each group died on the fourth postoperative day; Fisher's exact test, p = 0.763. Conclusions: Our research revealed that the heating of the anastomosis was not affected by the suturing technique performed.
Behavioral response of weaned pigs during gas euthanasia with CO2, CO2 with butorphanol, or nitrous oxide
(MDPI, 2020-04-27) Rault, Jean-Loup; Gates, Richard; Lay, Donald C.; Çavuşoğlu, Enver; Bursa Uludağ Üniversitesi/Veteriner Fakültesi/Zootekni Anabilim Dalı.; 0000-0002-9018-3511; 56541296300
Simple Summary Pig farmers are forced to euthanize a significant number of pigs due to injuries, hernias, or unthriftiness. The majority of pigs are euthanized using carbon dioxide gas asphyxiation. However, the humaneness of carbon dioxide is being increasingly questioned. An alternative is the use of nitrous oxide gas. We conducted this study to compare the euthanasia of young pigs using nitrous oxide or carbon dioxide. In addition, we tested the administration of a pain relief drug prior to carbon dioxide exposure to determine if we could eliminate behaviors indicative of pain. Pigs became unable to control their muscle movement, breathed heavily, and lost posture at the same time regardless of treatment. Pigs exposed to both gases showed heavy breathing and open-mouth breathing prior to losing posture. However, pigs exposed to carbon dioxide made more escape attempts but fewer squeals than pigs exposed to nitrous oxide. Administration of pain relief prior to exposure to carbon dioxide did not alter behaviors indicative of pain. The findings are inconclusive as to whether using nitrous oxide is significantly better than using carbon dioxide, but the results show that its use is just as effective, and possibly more humane. Abstract The swine industry is often forced to euthanize pigs in the first few weeks of life due to injuries, hernias, or unthriftiness. The majority of pigs are euthanized using carbon dioxide (CO2) gas asphyxiation but concerns as to the humaneness of CO2 are increasing. This study compared the euthanasia of weaned pigs using N2O (N2O; n = 9) or CO2 (n = 9), at 50% and 25% min(-1) exchange rate, respectively. In addition, we administered an analgesic prior to euthanasia with CO2 (CO2B) exposure as a third treatment (n = 9) to elucidate behaviors indicative of pain. Pigs in the CO2 and N2O treatments lost posture at similar times (latency of 145.0 +/- 17.3 and 162.6 +/- 7.0 s respectively, p > 0.10), while the CO2B treatment pigs lost posture the soonest (101.2 +/- 4.7 s, p < 0.01). The pigs in the CO2B treatment made more escape attempts than the CO2 or N2O pigs (16.4 +/- 4.2, 4.7 +/- 1.6, 0.3 +/- 0.2, respectively; p < 0.0004). However, pigs in N2O squealed more often than either the CO2 or CO2B pigs (9.0 +/- 1.6, 2.8 +/- 1.2, 1.3 +/- 0.6, respectively, p < 0.001). Given the similar time to loss of posture and shorter time displaying open mouth breathing, N2O may cause less stress to pigs; however, the greater number of squeals performed by these pigs suggests the opposite. It was not apparent that any behavior measured was indicative of pain. In conclusion, N2O applied at a 50% min(-1) flow rate can be an alternative to CO2 for pig euthanasia.
Bi-allelic mutations in M1AP are a frequent cause of meiotic arrest and severely impaired spermatogenesis leading to male infertility
(Cell Press, 2020-06-15) Temel, Şehime; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Tıbbi Genetik Anabilim Dalı.; 0000-0002-9802-0880; AAG-8385-2021; 6507885442
Male infertility affects similar to 7% of men, but its causes remain poorly understood. The most severe form is non-obstructive azoospermia (NOA), which is, in part, caused by an arrest at meiosis. So far, only a few validated disease-associated genes have been reported. To address this gap, we performed whole-exome sequencing in 58 men with unexplained meiotic arrest and identified the same homozygous frameshift variant c.676dup (p.Trp226LeufsTer4) in M1AP, encoding meiosis 1 associated protein, in three unrelated men. This variant most likely results in a truncated protein as shown in vitro by heterologous expression of mutant M1AP. Next, we screened four large cohorts of infertile men and identified three additional individuals carrying homozygous c.676dup and three carrying combinations of this and other likely causal variants in M1AP. Moreover, a homozygous missense variant, c.1166C>T (p.Pro389Leu), segregated with infertility in five men from a consanguineous Turkish family. The common phenotype between all affected men was NOA, but occasionally spermatids and rarely a few spermatozoa in the semen were observed. A similar phenotype has been described for mice with disruption of M1ap. Collectively, these findings demonstrate that mutations in M1AP are a relatively frequent cause of autosomal recessive severe spermatogenic failure and male infertility with strong clinical validity.
Bovine germinal vesicle oocyte and cumulus cell proteomics
(Bioscientifica, 2007-06) Memili, Erdoğan; Peddinti, Divyaswetha; Shack, L. Allen; Nanduri, Bindu; Mccarthy, Fiona M.; Burgess, Shane; Sağırkaya, Hakan; Uludağ Üniversitesi/Veteriner Fakültesi/Reprodüksiyon ve Suni Tohumlama Bölümü.; 6602400461
Germinal vesicle (GV) breakdown is fundamental for maturation of fully grown, developmentally competent, mammalian oocytes. Bidirectional communication between oocytes and surrounding cumulus cells (CC) is essential for maturation of a competent oocyte. However, neither the factors involved in this communication nor the mechanisms of their actions are well defined. Here, we define the proteomes of GV oocytes and their surrounding CC, including membrane proteins, using proteomics in a bovine model. We found that 4395 proteins were expressed in the CC and 1092 proteins were expressed in oocytes. Further, 858 proteins were common to both the CC and the oocytes. This first comprehensive proteome analysis of bovine oocytes and CC not only provides a foundation for signaling and cell physiology at the GV stage of oocyte development, but are also valuable for comparative studies of other stages of oocyte development at the molecular level. Furthermore, some of these proteins may represent molecular biomarkers for developmental potential of oocytes.
Brucella abortus L7/L12 recombinant protein induces strong Th1 response in acute brucellosis patients
(Shiraz Institute of Cancer Research, 2010-09) Oliveira, Sergio; Kazak, Esra; Göral, Güher; Akalın, Halis; Yılmaz, Emel; Heper, Yasemin; Oral, Haluk Barbaros; Uludağ Üniversitesi/Tıp Fakültesi/Enfeksiyon Hastalıkları ve Klinik Mikrobiyoloji Anabilim Dalı.; Uludağ Üniversitesi/Tıp Fakültesi/ Tıbbi Mikrobiyoloji Anabilim Dalı.; 0000-0003-0463-6818; K-7285-2012; AAG-8459-2021; AAH-6506-2021; AAU-8952-2020; 24921238200; 6603453166; 57207553671; 22037135100; 56191003300; 7004498001
Background: Because of high morbidity of the brucellosis in humans and the potential use of the microorganism as an agent of biologic warfare, protection of effective vaccines and specific diagnostic reagents become necessary to eradicate brucellosis. Objective: In this study we aimed to investigate the cytokine responses and changes in peripheral blood lymphocyte subgroups of acute brucellosis patients in response to L7/L12 and glyceraldehyde 3-phosphate dehydrogenase (GAPDH) recombinant proteins derived from Brucella abortus. Methods: levels of IFN-gamma, IL-4 and IL-10 secreted from PBMCs of 25 acute brucellosis patients and 15 healthy controls, stimulated with Phytohemagglutinin (PHA), L7/L12 or GAPDH were measured by ELISA. Furthermore alterations in lymphocyte subgroups in response to these Brucella antigens were determined by flow cytometry. Results: Extracellular IFN-gamma levels were found to be elevated after stimulation with L7/L12 in patients with acute brucellosis, whereas no significant changes were found in IL-4 and IL-10 levels. Similar data was also obtained with GAPDH, but the stimulation of IFN-gamma production was not observed in all patients and was not as strong as that observed for L7/L12. Moreover, when the distribution of lymphocytes subgroups (CD3(+), CD3(+)CD4(+), CD3(+)CD8(+), CD4(+)CD25(+), CD3(+)CD69(+) and CD3(+)CD152(+)) was evaluated, it was found that the stimulation with L7/L12 and GAPDH only led to an increase in the percentage of CD3(+)CD69(+) lymphocytes. Conclusion: These data indicate that Brucella abortus L7/L12 or GAPDH induce a Th1 type immune response in acute brucellosis patients. Additionally, these recombinant proteins, especially L7/L12, may be used in new vaccine preparations and diagnostic tests.

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